Regional distribution of cardiac output at rest and during exercise in patients with exertional angina pectoris before and after nifedipine therapy

The short-term effects of sublingual nifedipine (20 mg) on cardiac output and its distribution at rest and during exercise were evaluated by measurement of iliofemoral blood flow and cardiac output in 10 men with stable angina pectoris controlled by metoprolol. At rest, nifedipine significantly decreased iliofemoral vascular resistance from 294 +/- 36 to 165 +/- 29 dynes.s.cm-5.10(2) (p less than 0.01) and significantly increased iliofemoral blood flow from 0.34 +/- 0.04 to 0.57 +/- 0.11 liters/min (p less than 0.05). Systemic vascular resistance was reduced from 19 +/- 1 to 13 +/- 1 dynes.s.cm-5.10(2) (p less than 0.001) and cardiac output increased significantly from 4.7 +/- 0.3 to 5.8 +/- 0.5 liters/min (p less than 0.05). Mean arterial pressure decreased significantly and heart rate increased significantly. During maximal upright bicycle exercise during nifedipine therapy, iliofemoral vascular resistance and leg blood flow were unchanged compared with control (23 +/- 2 versus 21 +/- 3 dynes.s.cm-5.10(2) and 4.7 +/- 0.5 versus 4.4 +/- 0.6 liters/min), cardiac output remained significantly increased (12.8 +/- 0.8 to 15.2 +/- 1.2 liters/min, p less than 0.05) and systemic vascular resistance remained significantly reduced (8 +/- 1 to 5 +/- 1 dynes.s.cm-5.10(2); p less than 0.001). The proportion of cardiac output distributed to the working lower limbs was significantly reduced at all exercise levels. In summary, nifedipine caused a redistribution of cardiac output by vasodilating nonexercising vascular beds without altering the locally mediated vasodilation in exercising muscle. In patients with coronary artery disease given nifedipine therapy, an increase in exercise tolerance is due to relief of myocardial ischemia rather than to increased peripheral oxygen delivery.     

Effects of nifedipine on hemodynamics and cardiac function in patients with normal left ventricular ejection fraction already treated with propranolol

The interaction between nifedipine and propranolol on cardiac hemodynamics and function was investigated in 9 patients with normal left ventricular (LV) function who were undergoing cardiac catheterization for complaints of chest pain. Only 2 patients had angiographic evidence of significant coronary artery disease but no patient had clinical evidence of ischemia during the study. All patients were pre-treated with propranolol, 30 to 320 mg/day (mean +/- standard deviation 210 +/- 122); the propranolol serum level ranged from 43 to 246 ng/ml (mean 203 +/- 62). The administration of nifedipine resulted in a decrease in blood pressure (from 94 +/- 11 to 85 +/- 13 mm Hg, p less than 0.05), increase in heart rate (from 59 +/- 6 to 65 +/- 7 beats/min, p less than 0.05), and an increase in both mean right atrial and mean pulmonary artery wedge pressures (from 8 +/- 3 to 9 +/- 3 mm Hg and from 13 +/- 3 to 14 +/- 4 mm Hg, respectively, both p less than 0.05). Cardiac index increased (from 2.3 +/- 0.3 to 2.7 +/- 0.2 liters/min/m2, p less than 0.01). Stroke volume index also increased significantly (from 39 +/- 5 to 43 +/- 6 ml/m2) and systemic vascular resistance decreased (from 1,715 +/- 369 to 1,255 +/- 271 dynes s cm-5, p less than 0.01). No significant change was noted in pulmonary vascular resistance (148 +/- 94 vs 140 +/- 62 dynes s cm-5), LV stroke work index (44 +/- 9 vs 42 +/- 10 g-m/m2), LV end-diastolic pressure (15 +/- 2 vs 16 +/- 2 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)     

Sublingual nifedipine: acute effects in severe chronic congestive heart failure secondary to idiopathic dilated cardiomyopathy

Nine patients with chronic, severe (New York Heart Association class III to IV) congestive heart failure were studied to determine the acute effects of 10 mg of sublingual nifedipine on left ventricular (LV) function. Hemodynamic and echocardiographic data were obtained at rest and 30 minutes, 1, 2, 4 and 6 hours after nifedipine. Measurements at rest reflected LV dysfunction with elevation of end-diastolic volume index (102 +/- 46 ml/m2), pulmonary capillary wedge pressure (17 +/- 8 mm Hg), systemic vascular resistance (1,547 +/- 439 dynes s cm-5) and reduction of cardiac index (2.8 +/- 0.5 liters/min/m2). There were no adverse effects noted with administration of sublingual nifedipine. Initial changes through 1 hour reflected an unloading effect of nifedipine with reduction in pulmonary capillary wedge pressure (11 +/- 5 mm Hg) (p less than 0.05), systemic vascular resistance (1,179 +/- 289 dynes s cm-5) (p less than 0.01), end-diastolic volume index (91 +/- 37 ml/m2 [difference not significant]) and an increase in cardiac index (3.6 +/- 0.7 ml liters/min/m2) (p less than 0.01). Subsequently the cardiac index, systemic vascular resistance and end-diastolic volume index returned toward baseline. Only the pulmonary capillary wedge and pulmonary artery pressures demonstrated a sustained reduction through the 6-hour study period suggesting an effect of nifedipine on LV relaxation. Thus, sublingual nifedipine administered acutely to patients with clinical congestive heart failure is a safe and efficacious vasodilator.     

Central and renal hemodynamic effects of a new agonist at peripheral dopamine- and beta-2 adrenoreceptors (dopexamine) in patients with heart failure

The effect of dopexamine, a new dopamine analogue, on central and renal hemodynamics was evaluated in nine patients with chronic, congestive heart failure caused by severe left ventricular (LV) systolic dysfunction. The administration of the maximally tolerated dose (7.2 +/- 4 micrograms/kg/min) resulted in a significant increase in cardiac index from 1.9 +/- 0.4 L/min/m2 to 2.6 +/- 0.9 L/min/m2 (p less than 0.05). This increase in cardiac index was largely a result of increase in heart rate (from 88 +/- 20 beats/min to 104 +/- 24 beats/min, p less than 0.05), because stroke volume index demonstrated only a small change (from 23 +/- 10 ml/m2 to 27 +/- 11 ml/m2, p not significant) in spite of a significant fall in systemic vascular resistance from 1992 +/- 717 dynes.sec.cm-5 to 1361 +/- 524 dynes.sec.cm-5 (p less than 0.05) and diastolic blood pressure (from 89 +/- 15 mm Hg to 80 +/- 17 mm Hg, p less than 0.05). No change was seen during dopexamine infusion in systolic blood pressure, right and left ventricular filling pressures, and LV stroke work index. Both renal blood flow and glomerular filtration rate were impaired at baseline in most patients. Dopexamine administration resulted in a significant increase (2x coefficient of variation) in renal blood flow in two patients only. Mean values of both renal blood flow and glomerular filtration rate did not show significant change (485 +/- 183 ml/min vs 563 +/- 221 ml/min and 89 +/- 39 ml/min vs 93 +/- 34 ml/min, respectively, p not significant).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of prostacyclin and prazosin in the treatment of congestive heart failure; with special reference to the sympathetic nervous system

Therapy to decrease the load in congestive heart failure is now classified as acute and chronic vasodilator therapy. In this symposium, we presented prostacyclin (PG I2) as an acute and prazosin as a chronic vasodilator. Their hemodynamic and clinical effectiveness were evaluated and their effect on the sympathetic nervous system was also studied. We studied the effect of intravenous prostacyclin infusion in doses of 22 +/- 11 ng/kg/min in nine patients with severe congestive heart failure refractory to digitalis and diuretic drugs. After prostacyclin infusion, mean pulmonary capillary wedge pressure decreased from 21.0 +/- 7.9 to 15.0 +/- 6.6 mmHg (p less than 0.001), mean arterial pressure from 98.9 +/- 12.8 to 76.2 +/- 7.0 mmHg (p less than 0.001), systemic vascular resistance from 2,574 +/- 384 to 1,368 +/- 283 dynes X sec X cm-5 (p less than 0.001), pulmonary vascular resistance from 1,008 +/- 451 to 443 +/- 135 dynes X sec X cm-5 (p less than 0.001) and pulmonary arteriolar resistance from 330 +/- 111 to 189 +/- 73 dynes X sec X cm-5 (p less than 0.001). The cardiac index increased from 2.0 +/- 0.37 to 3.2 +/- 0.59 l/min/m2 (p less than 0.001), and the stroke index from 27.6 +/- 8.69 to 42.0 +/- 0.62 ml/m2 (p less than 0.001). Moreover, prostacyclin therapy counteracted the sensation of coldness of the limbs and face, and patients felt warmth and mild flushing of the face. The effect of prazosin on the exercise duration time until dyspnea was evaluated by the treadmill test.(ABSTRACT TRUNCATED AT 250 WORDS)     

Coronary and systemic hemodynamic effects of nicardipine

Systemic and coronary hemodynamic effects of a new dihydropyridine calcium antagonist, nicardipine, were studied in 15 patients. Nicardipine was administered as a 2-mg bolus intravenously followed by an infusion titrated to maintain a 10 to 20-mm Hg decrease in systolic pressure. Nicardipine increased both heart rate from 69 +/- 3 to 81 +/- 3 beats/min and cardiac output from 7.3 +/- 0.5 to 9.9 +/- 0.5 liters/min (both p less than 0.001) as systemic vascular resistance decreased from 1,183 +/- 70 to 733 +/- 33 dynes s cm-5 (p less than 0.001). Left ventricular end-diastolic pressure remained constant, at 14 +/- 1 vs 14 +/- 1 mm Hg as stroke volume increased from 108 +/- 6 to 123 +/- 6 ml/m2 (p less than 0.001). Coronary blood flow increased from 102 +/- 9 to 147 +/- 13 ml/min, while coronary resistance decreased from 1.17 +/- 0.1 to 0.7 +/- 0.1 mm Hg/ml/min (both p less than 0.001). Heart rate-systolic blood pressure product did not change (104 +/- 5 vs 106 +/- 5 beats/min mm Hg X 10(-2), difference not significant) with drug administration. At the same heart rate before and during nicardipine administration (using atrial pacing in 6 patients), significant augmentation of coronary flow was still observed. Thirteen of 14 patients showed a greater percent decrease in coronary resistance than systemic vascular resistance. Nicardipine differs from other calcium antagonists with respect to consistent augmentation of coronary blood flow. This effect appears to be the result, in part, of increased potency in the coronary bed compared with the systemic vascular bed.     

Static exercise with congestive heart failure and the response to vasodilating drugs

The hemodynamic response to static exercise in 28 patients with congestive heart failure (CHF) was compared with that in 8 control subjects. Static handgrip exercise at 50% of the maximal voluntary contraction was performed to fatigue. In patients with CHF, pulmonary arterial wedge pressure increased from 20 +/- 18 to 31 +/- 10 mm Hg (p less than 0.001) (mean +/- standard deviation) and systemic vascular resistance increased from 1,730 +/- 454 to 2,151 +/- 724 dynes s cm-5 (p less than 0.001). Although cardiac index did not change significantly, stroke volume index and stroke work index decreased from 24 +/- 6 to 20 +/- 6 ml/m2 (p less than 0.001) and 28 +/- 11 to 25 +/- 12 g-m/s2 (p less than 0.05), respectively. In control subjects, pulmonary arterial wedge pressure did not change significantly; cardiac index increased from 3.6 +/- 0.3 to 4.0 +/- 0.4 liters/min/m2 (p less than 0.05) and systemic vascular resistance increased slightly, from 1,011 +/- 186 to 1,106 +/- 180 dynes s cm-5 (p less than 0.05). The effects of arterial dilation with hydralazine on the response to static exercise were assessed in 10 of the patients with CHF. Compared with predrug exercise, cardiac index increased 68% (p less than 0.01), stroke volume index increased 76% (p less than 0.01) and systemic vascular resistance decreased 47% (p less than 0.01) after administration of hydralazine. Thus, static exercise can have adverse effects on cardiac performance in patients with CHF.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of intravenous and intracoronary nicardipine

The systemic and coronary hemodynamic effects of nicardipine, a calcium antagonist, were studied in 30 patients. Increased coronary blood flow (from 102 +/- 9 to 147 +/- 13 ml/min; p less than 0.001), heart rate (from 69 +/- 3 to 81 +/- 3 beats/min; p less than 0.001), stroke volume (108 +/- 6 to 123 +/- 6 ml; p less than 0.001) and cardiac output (from 7.3 +/- 0.5 to 9.9 +/- 0.5 liters/min; p less than 0.001) were demonstrated in 15 patients administered intravenous nicardipine (2 mg bolus given over 1 minute, followed by infusion of 50 micrograms/min to maintain 10 to 20 mm Hg decrease in systolic blood pressure). Systemic vascular resistance decreased (from 1,183 +/- 70 to 733 +/- 33 dynes s cm-5) as did coronary resistance (from 1.47 +/- 0.1 to 0.7 +/- 0.1 mm Hg/ml/min; p less than 0.001). Other hemodynamic parameters such as left ventricular end-diastolic pressure, stroke volume and work, aortic blood flow and acceleration, ejection and external power, myocardial oxygen consumption and time constant for left ventricular isovolumic relaxation also were evaluated. To distinguish between direct myocardial effects of nicardipine and peripheral effects, 15 patients were given intracoronary nicardipine (0.1 or 0.2 mg) during cardiac catheterization. Nicardipine produced slight depression of left ventricular contractile function and impairment of left ventricular relaxation; but these changes were mild and transient compared with the marked and sustained increase in coronary blood flow that persisted 7 minutes after administration. Thus, nicardipine is a relatively selective vasodilator with minimal direct myocardial depressant activity n humans.     

MDL 17,043: short- and long-term cardiopulmonary and clinical effects in patients with heart failure

MDL 17,043, an inotropic and vasodilator drug, is believed to have beneficial effects in patients with heart failure. Its short- and long-term hemodynamic and cardiopulmonary effects were studied in 10 patients with New York Heart Association functional class III heart failure who were maintained on digitalis and diuretic drugs. Hemodynamics at baseline study and after 24 hours of oral therapy (four doses of 6 mg/kg) showed increased cardiac output (3.9 +/- 0.7 to 6.1 +/- 1.1 liters/min, p less than 0.05), increased stroke volume (42 +/- 12 to 60 +/- 15 ml, p less than 0.05), decreased systemic vascular resistance (1,564 +/- 326 to 1,009 +/- 296 dynes X s X cm-5, p less than 0.05) but no change in pulmonary capillary wedge pressure (31 +/- 6 to 25 +/- 13 mm Hg, p = NS). Only systemic vascular resistance and arteriovenous oxygen difference were significantly decreased during exercise. When restudied after 5 weeks of therapy, neither cardiac output nor stroke volume showed a sustained increase at rest or during exercise, and effects on systemic vascular resistance and arteriovenous oxygen difference were not sustained at exercise (p = NS). Peak oxygen uptake during exercise was 8.1 +/- 2.5 ml/kg per min at baseline and was not significantly increased either acutely (9.2 +/- 2.4 ml/kg per min, p = NS) or chronically (8.9 +/- 2.2 ml/kg per min, p = NS). Problems of increased ventricular arrhythmias and diarrhea were noted after therapy was begun.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of diltiazem and long-term beta 1-adrenergic blockade on hemodynamics and blood flow during exercise in patients with stable angina pectoris

The short-term effects of oral diltiazem on hemodynamics and distribution of cardiac output at rest and during semiupright bicycle exercise were evaluated in eight patients with stable effort angina on long-term beta 1-adrenergic blockade. Cardiac output and iliofemoral blood flow were measured using thermodilution. The patients were exercised to the same work load on a bicycle before and 2 h after oral diltiazem (60 mg in two patients and 120 mg in six). At maximal exercise, diltiazem reduced heart rate from 94 +/- 5 to 88 +/- 6 beats/min (p less than 0.01), mean arterial pressure from 139 +/- 5 to 127 +/- 4 mm Hg (p less than 0.01) and systemic vascular resistance from 9.7 +/- 0.7 to 8.4 +/- 0.4 x 10(2) dynes.s.cm-5 (p less than 0.05) compared with control. During exercise, cardiac output, iliofemoral blood flow, mean pulmonary wedge pressure and mean right atrial pressure were not altered, but stroke volume increased from 119 +/- 11 to 131 +/- 10 ml (p less than 0.05). Maximal ST segment depression during exercise was decreased and angina was less. Diltiazem does not alter the distribution of the cardiac output during exercise but improves ischemia.     

Effects of alpha human atrial natriuretic polypeptide on the systemic hemodynamics and coronary circulation in patients with ischemic heart disease

Alpha human atrial natriuretic polypeptide (alpha-hANP) was intravenously infused into 7 patients with ischemic heart disease who had almost normal cardiac function at a rate of 0.025 micrograms/kg/min for 15 min. During infusion of alpha-hANP, left ventricular (LV) systolic pressure decreased from 144 +/- 19 (SD) to 129 +/- 22 mmHg (p less than 0.01), LV end diastolic pressure (EDP) from 15 +/- 5 to 13 +/- 4 mmHg (p less than 0.05), mean aortic pressure from 102 +/- 14 to 91 +/- 14 mmHg (p less than 0.01), time constant of LV pressure fall (T) from 100 +/- 15 to 88 +/- 13 msec (p less than 0.05), systemic vascular resistance (SVR) from 1711 +/- 206 to 1424 +/- 340 dynes.sec.cm-5 (p less than 0.05) and coronary vascular resistance (CVR) from 8.5 +/- 1.2 to 7.4 +/- 1.3 x 10(4) dynes.sec.cm-5 (p less than 0.05). There was a linear correlation between percent changes in SVR and those of CVR (r = 0.92, p less than 0.01), and the fall in CVR was approximately 68% of that in SVR. Increases occurred in heart rate from 63 +/- 7 to 66 +/- 8 beats/min (p less than 0.05), LV dp/dt from 1558 +/- 266 to 1627 +/- 238 mmHg/sec (p less than 0.05), LV dp/dt/p from 22.9 +/- 3.2 to 25.6 +/- 3.7/sec (p less than 0.01), and myocardial oxygen consumption (from 7.9 +/- 2.4 to 9.8 +/- 2.1 ml/min, p less than 0.05), while mean right atrial and mean pulmonary arterial pressures and pulmonary vascular resistance were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic effects of nifedipine on secondary pulmonary hypertension in man

We evaluated the hemodynamic effects of the calcium antagonist nifedipine in 13 consecutive patients admitted to the intensive care unit with secondary pulmonary hypertension. Etiology of secondary pulmonary hypertension was: chronic obstructive pulmonary disease (n = 9), pulmonary emboli (n = 2), pulmonary fibrosis (n = 2). We obtained the resting hemodynamic parameters before, and 60, 120, 180 minutes after the sublingual administration of nifedipine 20 mg. All patients had normal pulmonary artery wedge pressure before nifedipine. After 60 minutes, systolic pulmonary artery pressure fell from 72.3 +/- 7 to 57.3 +/- 5.4 mm Hg (p less than 0.005) and mean pulmonary artery pressure from 44.6 +/- 4.0 to 33.6 +/- 3.2 mm Hg (p less than 0.001). Cardiac output rose from 6.36 +/- 0.56 to 7.65 +/- 0.64 l/min (p less than 0.005). The pulmonary vascular resistance fell from 431 +/- 58 to 238 +/- 36 dynes. sec. cm-5 (p less than 0.001). Heart rate, mean systemic arterial pressure, pulmonary artery wedge pressure, total systemic vascular resistance and arterial partial pressure of O2 (PaO2) remained unchanged. In this heterogenous population we were unable to reproduce the results of other authors, showing a correlation between PaO2 and fall of pulmonary vascular resistance. These findings confirm the pulmonary vasodilating effect of nifedipine in patients with secondary pulmonary hypertension.     

Combined hemodynamic effects of nifedipine and nitroglycerin in congestive heart failure

To determine if the addition of preload reduction with nitrates would potentiate the acute vasodilator actions of nifedipine, we titered intravenous nitroglycerin in seven patients with severe congestive heart failure after they received a single oral dose of nifedipine. The peak hemodynamic effect of nifedipine occurred at 30 minutes, with large reductions of systemic vascular resistance (1831 +/- 128 to 1132 +/- 154 dynes X sec X cm-5; p less than 0.001) and mean arterial pressure (87 +/- 7 to 71 +/- 7 mm Hg; p less than 0.01). This was associated with an increase of stroke volume index from 22 +/- 3 to 27 +/- 3 ml/m2 (p less than 0.01) but no significant changes in heart rate, right atrial pressure, or pulmonary wedge pressure. These hemodynamic changes were attenuated over a 2-hour observation period. At 2 hours, the addition of intravenous nitroglycerin resulted in large reductions in right atrial pressure (9 +/- 2 to 6 +/- 1; p less than 0.01) and pulmonary wedge pressure (23 +/- 2 to 17 +/- 2; p less than 0.001). This was associated with further increases in cardiac index (from 1.99 +/- .15 to 2.25 +/- .14 L/min/m2; p less than 0.001) and stroke volume index (26 +/- 3 to 29 +/- 3 ml/m2; p less than 0.01). Thus, the addition of nitroglycerin to nifedipine will optimize preload reduction and enhance the vasodilator action of nifedipine. Further controlled studies are necessary to determine the long-term hemodynamic effects and the clinical role of nifedipine and its combination with nitrates in patients with severe congestive heart failure.     

Hemodynamic effects of intravenous isosorbide dinitrate and nitroglycerine in acute myocardial infarction and elevated pulmonary artery wedge pressure

We compared in a randomized fashion the hemodynamic effects of intravenous (IV) isosorbide dinitrate (ISDN) and nitroglycerine (NTG) in 45 patients with acute myocardial infarction and elevated pulmonary artery wedge pressure (Paw). Titration of ISDN dose to lower Paw greater than or equal to 25 percent resulted in a fall of this parameter from 32 +/- 8 to 24 +/- 5 mm Hg and was associated with a fall in mean blood pressure (96 +/- 15 to 90 +/- 14 mm Hg, p less than 0.05), systemic vascular resistance (1715 +/- 572 to 1548 +/- 414 dynes X s X cm-5, (p less than 0.05), pulmonary vascular resistance (182 +/- 106 to 154 +/- 78 dynes X s X cm-5, p less than 0.05) and mean right atrial pressure (11 +/- 4 to 7 +/- 4 mm Hg, p less than 0.05). In addition, ISDN significantly (p less than 0.05) increased cardiac index from 2.37 +/- 0.54 to 2.54 +/- 0.59 L/min/m2, stroke volume index from 28 +/- 8 to 31 +/- 8 ml/m2, and stroke work index from 28 +/- 11 to 31 +/- 12 g X m/m2. The ISDN dose ranged from 50 to 533 micrograms/min (mean +/- SD 326 +/- 176 micrograms/min) and could not be predicted from baseline hemodynamic values. A comparison between the effect of ISDN and NTG in doses producing comparable reduction in Paw showed similar hemodynamic changes. It was concluded that IV ISDN in patients with elevated mean pulmonary artery wedge pressure due to acute myocardial infarction results in a decrease in right and left ventricular preload and afterload and improvement of cardiac output and cardiac work. The effective dose ranges from 50 to 533 micrograms/min and cannot be predicted from baseline hemodynamic values. In doses producing comparable reduction in Paw, ISDN and NTG had similar hemodynamic effects.     

Effects of sublingual nifedipine on hemodynamics and systolic and diastolic function in patients with hypertrophic cardiomyopathy

The hemodynamic effects of sublingual nifedipine were examined in 36 patients with hypertrophic cardiomyopathy. Twenty-one patients were initially given 20 mg and 15 patients were given 10 mg of the drug; 30 min after this first dose 26 patients received 10 mg and one patient 20 mg as a second dose. Hemodynamic findings in patients who received different doses of the drug were similar. Peak effects included an increase in heart rate from 79 +/- 12 to 91 +/- 14 (mean +/- 1 SD) beats/min (p less than .01), and a decrease in mean blood pressure from 89 +/- 12 to 77 +/- 10 mm Hg (p less than .01). Cardiac index increased after nifedipine (2.8 +/- 0.6 to 3.3 +/- 0.8 liters/min/m2; p less than .01); stroke volume index, however, did not change (36 +/- 7 to 36 +/- 8 ml/beat/m2; NS). Peripheral vascular resistance index fell significantly from 822 +/- 261 to 610 +/- 197 dynes X sec X cm-5 (p less than .01). Overall, left ventricular outflow tract gradient (LVOTG) did not change in patients with significant (greater than or equal to 30 mm Hg) basal LVOTG (75 +/- 22 to 83 +/- 22 mm Hg; NS), but it increased significantly in those six patients in whom peripheral vascular resistance fell by 25% or more (73 +/- 28 to 99 +/- 22 mm Hg; p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic effects of infused arginine vasopressin in congestive heart failure

The hemodynamic effects of exogenously administered arginine vasopressin were assessed in 11 patients with chronic congestive heart failure. Infusion rates of 0.1 to 0.8 pmol/kg per min increased plasma arginine vasopressin from 6.5 +/- 2.7 (SD) pg/ml at control to 63 +/- 39 pg/ml at the highest infusion rate. There were progressive decreases in cardiac output and stroke volume, with increases in systemic vascular resistance and pulmonary capillary wedge pressure, but only minimal changes in heart rate and blood pressure. Changes in cardiac output, stroke volume and systemic resistance were evident from the first infusion rate, which increased plasma arginine vasopressin from 6.5 +/- 2.7 to 9.9 +/- 4.6 pg/ml. A paired analysis of baseline hemodynamic data with those measured during infusions producing an arginine vasopressin level averaging 15 +/- 2.6 pg/ml yielded the following changes: cardiac output decreased from 4.6 +/- 1.2 to 4.2 +/- 0.96 liters/min (p less than 0.01), stroke volume decreased from 60 +/- 19 to 54 +/- 16 ml (p less than 0.005) and systemic vascular resistance increased from 1,329 +/- 396 to 1,443 +/- 395 dynes X s X cm-5 (p = 0.01). Thus, small increases in circulating arginine vasopressin cause modest but significant adverse circulatory effects in patients with congestive heart failure. A fall in cardiac output, probably as a result of increased afterload, is seen at levels of arginine vasopressin within the basal range found in congestive heart failure. These data demonstrate that circulating arginine vasopressin in physiologic concentrations is capable of influencing hemodynamics in patients with congestive heart failure and suggest that therapy for this condition directed at inhibition of the vascular effect of arginine vasopressin may be potentially useful.     

Treatment of primary pulmonary hypertension with nifedipine. A hemodynamic and scintigraphic evaluation

To evaluate the potential value of nifedipine treatment for primary pulmonary hypertension, hemodynamic and scintigraphic measurements were made before and 15 to 30 minutes after nifedipine, 10 to 20 mg, was given sublingually to nine patients. Nifedipine treatment increased cardiac output (mean +/- SD, 3.6 +/- 1.7 to 5.3 +/- 2.8 L/min, p less than 0.001) and decreased mean aortic pressure (99 +/- 19 to 85 +/- 12 mm Hg, p less than 0.001) and total pulmonary and total systemic resistances (1605 +/- 787 to 1025 +/- 540 dyn X s X cm-5 and 2761 +/- 1557 to 1591 +/- 823 dyn X s X cm-5, respectively; p less than 0.005). Heart rate and mean pulmonary arterial pressure did not change significantly. Right ventricular end-diastolic volume decreased 10% (p = 0.01), end-systolic volume decreased 15% (p less than 0.01), and right ventricular ejection fraction increased 18% (p less than 0.05) in eight patients. After 4 to 14 months (mean, 7.3 +/- 3.8) of treatment with nifedipine, 40 to 120 mg/d, in six patients, cardiac output increased (3.6 +/- 2.0 to 5.0 +/- 1.8 L/min, p less than 0.01) and total pulmonary resistance decreased (1572 +/- 730 to 987 +/- 586 dyn X s X cm-5, p = 0.025), whereas pulmonary arterial pressure remained unchanged (59 +/- 23.2 to 55 +/- 28.6 mm Hg, p greater than 0.05) compared with baseline values. We conclude that nifedipine therapy may be useful in the chronic management of patients with primary pulmonary hypertension.     

Systemic vasoconstrictor effects of oxygen administration in obliterative pulmonary vascular disorders

Although oxygen is frequently administered to patients with obliterative pulmonary vascular disorders (OPVD) for diagnostic and therapeutic purposes, its hemodynamic effects in these patients have not been systematically evaluated. The response to administration of 50 to 70% oxygen was studied in 14 patients with pulmonary hypertension secondary to OPVD. Mean pulmonary artery pressure decreased (from 62 +/- 5 to 57 +/- 5 mm Hg, p less than 0.01) after oxygen inhalation secondary to a decrease in cardiac index (1.9 +/- 0.2 to 1.8 +/- 0.2 liters/min/m2, p less than 0.01), without changes in pulmonary arteriolar resistance. This decline in forward output appeared to result from a systemic vasoconstrictor effect of oxygen (change in systemic vascular resistance from 1,965 +/- 275 to 2,297 +/- 336 dynes s cm-5, p less than 0.01), which decreased heart rate (from 93 +/- 3 to 89 +/- 2 beats/min, p less than 0.01) by stimulation of baroreceptor reflexes and decreased stroke volume (from 22 +/- 3 to 21 +/- 2 ml/beat/m2, p less than 0.05) by increasing impedance to left ventricular ejection. The decrease in left-sided cardiac output likely led to a decline in venous return to the right side of the heart and, consequently, to a decrease in right atrial and pulmonary arterial pressures. Accordingly, the percent decrease in mean pulmonary artery pressure varied linearly and directly with the percent increase in systemic vascular resistance (r = 0.84), but not with changes in pulmonary arteriolar resistance (r = 0.15).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of nisoldipine on systemic and leg blood flow, oxygen transport and metabolism, and hemodynamics during exercise in effort angina pectoris

The acute effects of 10 mg of oral nisoldipine on hemodynamics, oxygen transport and metabolism, and distribution of cardiac output, at rest and during semiupright bicycle exercise, were evaluated in 10 men with effort angina receiving long-term beta 1 blockade. Cardiac output and leg blood flow were measured using the thermodilution technique. At rest, nisoldipine decreased systemic resistance from 18.9 +/- 1.0 to 15.9 +/- 1.2 dynes.s.cm-5.10(2) (p less than 0.05) and cardiac output increased from 4.8 +/- 0.2 to 5.3 +/- 0.3 liters/min (p less than 0.05) without changing leg blood flow. During maximal exercise with nisoldipine, systemic resistance was reduced (10.6 +/- 0.9 to 8.6 +/- 0.5 dynes.s.cm-5.10(2), p less than 0.05) and cardiac output increased 18% (10.3 +/- 0.7 to 12.2 +/- 0.6 liters/min, p less than 0.05) when compared with control values. Exercise heart rate was higher with nisoldipine (113 +/- 4 vs 106 +/- 4 beats/min, p less than 0.01), but the mean arterial pressure was not significantly changed, giving a higher rate-pressure product. The increase in mean pulmonary artery wedge pressure was attenuated (26 +/- 3 vs 30 +/- 3 mm Hg during control exercise, p less than 0.05), but ST depression was unaltered. Exercise leg flow was reduced by nisoldipine from 4.3 +/- 0.4 to 3.9 +/- 0.3 liters/min (p = 0.07) and the proportion of cardiac output distributed to the legs was reduced from 42 +/- 3 to 33 +/- 3% (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Long-term treatment of severe cardiac insufficiency with captopril

23 patients with a mean age of 62 +/- 7 years and suffering from a cardiomyopathy with severe chronic heart failure (16 patients in stage IV of the New York Association (NYHA) classification and 7 in stage III NYHA) received long term treatment with captopril (9 patients received 75 mg/day, 9 received 150 mg/day and 5 received 300 mg/day) with a follow-up of 12 +/- 9 months. Following the acute administration of captopril, there was an increase in the cardiac index (Cl) (2.76 +/- 0.56 vs 2.10 +/- 0.4 l . min-1 . m-2, p less than 0.001) between the 4th and 6th hour, a significant decrease in peripheral resistance (PR) (1416 +/- 304 vs 1094 +/- 406 dynes/s/cm-5, p less than 0.001), total pulmonary resistance (TPR) (537 +/- 228 vs 660 +/- 258 dynes/s/cm-5, p less than 0.01) and pulmonary diastolic pressure (PDP) (15.4 +/- 7.2 vs 18.6 +/- mm Hg, p less than 0.001). An early (3rd day) and reversible renal failure caused the treatment to be suspended in one patient. In the 22 other patients, a marked and lasting clinical improvement was obtained (18 patients with stage II NYHA and 4 with stage III NYHA). The beneficial haemodynamic effects persisted until the 4th month in 14 patients (Cl: 2.38 +/- 0.4 vs 2.10 +/- 0.4 l . min-1 . m-2, p less than 0.1; PR: 1828 +/- 314 vs 2054 +/- 406 dynes/s/cm-5, p less than 0.01; TPR: 526 +/- 284 vs 660 +/- 258 dynes/s/cm-5, p less than 0.01; PDP: 16.8 +/- 8.7 vs 18.6 +/- 8.6 mmHg, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)